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Pieter C Dagnelie

Publications and source records attributed to Pieter C Dagnelie.

At least 19 recordsLinked to original sources

Application of adenosine 5'-triphosphate (ATP) infusions in palliative home care: design of a randomized clinical trial.

BACKGROUND: Palliative care in cancer aims at alleviating the suffering of patients. A previous study in patients with advanced non-small-cell lung cancer showed that adenosine 5'-triphosphate (ATP) infusions had a favourable effect on fatigue, appetite, body weight, muscle strength, functional status and quality of life. The present study was designed 1. To evaluate whether ATP has favourable effects in terminally ill cancer patients, 2. To evaluate whether ATP infusions may reduce family caregiver burden and reduce the use of professional health care services, and 3. To test the feasibility of application of ATP infusions in a home care setting. METHODS/DESIGN: The study can be characterized as an open-labelled randomized controlled trial with two parallel groups. The intervention group received usual palliative care, two visits by an experienced dietician for advice, and regular ATP infusions over a period of 8 weeks. The control group received palliative care as usual and dietetic advice, but no ATP. This paper gives a description of the study design, selection of patients, interventions and outcome measures. DISCUSSION: From April 2002 through October 2006, a total of 100 patients have been randomized. Follow-up of patients will be completed in December 2006. At the time of writing, five patients are still in follow up. Of the 95 patients who have completed the study, 69 (73%) have completed four weeks of follow-up, and 53 (56%) have completed the full eight-week study period. The first results are expected in 2007.

Adenosine Triphosphate↗

Early life exposure to antibiotics and the subsequent development of eczema, wheeze, and allergic sensitization in the first 2 years of life: the KOALA Birth Cohort Study.

OBJECTIVES: Antibiotic exposure in early life may be associated with atopic disease development either by interfering with bacterial commensal flora or by modifying the course of bacterial infections. We evaluated early life exposure to antibiotics and the subsequent development of eczema, wheeze, and allergic sensitization in infancy. METHODS: Information on antibiotic use in the first 6 months and eczema and wheeze until age 2 was collected by repeated questionnaires in 2764 families participating in the KOALA (Child, Parent and Health: Lifestyle and Genetic Constitution [in Dutch]) Birth Cohort Study in The Netherlands. Antibiotic intake was evaluated both as maternal antibiotic use during breastfeeding and infant oral medication. Venous blood samples taken from 815 infants at 2 years of age were analyzed for total and specific immunoglobulin E against common food and inhalant allergens using a radioallergosorbent test. Multivariate logistic regression analysis was used to adjust for confounding factors. RESULTS: During the first 2 years, eczema was present in 32% of all infants, recurrent wheeze in 11%, and prolonged wheezing in 5%. At 2 years old, 27% of children were sensitized against > or = 1 allergen. At 6 months old, 11% had been exposed to antibiotics through breast milk and 20% directly through medication. The risk for recurrent wheeze, and prolonged wheeze was higher in infants directly exposed to antibiotics through medication, also after excluding from the analyses children who wheezed in the same period as an antibiotic had been used (avoiding reverse causation). Antibiotic use through breastfeeding was associated with recurrent wheeze, but prolonged wheeze was not. Eczema and sensitization were not associated with antibiotic exposure. CONCLUSIONS: We demonstrated that early antibiotic use preceded the manifestation of wheeze but not eczema or allergic sensitization during the first 2 years of life. Different biological mechanisms may underlie the etiology of wheeze compared with eczema or sensitization. Antibiotic exposure through breastfeeding enhanced the risk for recurrent wheeze, but this needs further confirmation.

Anti-Bacterial Agents↗

Purinergic receptors involved in the immunomodulatory effects of ATP in human blood.

We recently showed that the physiological compound ATP simultaneously inhibited TNF-alpha and stimulated IL-10 release in LPS-PHA stimulated blood. The purpose of the present study was to determine the mechanism involved in the concerted modulatory effect of ATP on TNF-alpha and IL-10. Incubation of blood with ATP in the presence of selective P2 receptor antagonists showed that the stimulatory effect of ATP on IL-10 release was completely annihilated by both 2-MeSAMP (a P2Y12/13 receptor antagonist) and PSB-0413 (a P2Y12 receptor antagonist). On the other hand, the inhibitory effect of ATP on TNF-alpha release was completely reversed by 5'-AMPS (a P2Y11 receptor antagonist) as well as by H-89, an inhibitor of cAMP-activated PKA. The concerted inhibition by ATP of TNF-alpha release via P2Y11 activation and stimulation of IL-10 release via P2Y12 activation implicates a novel approach towards immunomodulation by altering the balance among pro- and anti-inflammatory cytokines.

Adenosine Triphosphate↗

Psychometric properties of the revised Piper Fatigue Scale in Dutch cancer patients were satisfactory.

OBJECTIVE: To examine the psychometric properties of the revised Piper Fatigue Scale (PFS) in Dutch cancer patients. STUDY DESIGN AND SETTING: Participants were 64 patients with lung (any stage, nonsurgery) and breast (any stage) cancer, selected for curative high-dose radiotherapy (> or =50 Gy). Prior to radiotherapy, patients completed the revised PFS (translated into Dutch), the Multidimensional Fatigue Inventory (MFI), and the Rotterdam Symptom Checklist (RSCL). Reliability and construct and criterion validity of the PFS were investigated. RESULTS: Overall, the structure of the Dutch revised PFS appeared appropriate, with corrected item-subscale correlations being higher than the correlations of the same item with the three other subscales; furthermore, internal consistency was excellent (Cronbach's alpha > or =0.90). Lung cancer patients were significantly more tired then breast cancer patients, supporting construct validity. Criterion validity was also satisfactory, with highest correlations of PFS total fatigue with the MFI subscale general fatigue (0.84) and RSCL overall quality of life score (0.74). Internal consistency was similar in Dutch and U.S. breast cancer patients; fatigue scores were lower on several PFS subscales in the Dutch study population. CONCLUSION: Psychometric properties of the Dutch version of the revised PFS, as tested in cancer patients prior to radiotherapy, were satisfactory.

Adult↗

ATP inhibits hydroxyl radical formation and the inflammatory response of stimulated whole blood even under circumstances of severe oxidative stress.

We recently reported that Adenosine-5'-triphosphate (ATP) is able to inhibit the inflammatory reaction in stimulated whole blood. Many diseases, in which inflammatory reactions are involved, are associated with oxidative stress. In the present study, we therefore, investigated the effect of ATP on cytokine release in stimulated whole blood under conditions of oxidative stress, as simulated by pre-incubation of blood with hydrogen peroxide (H(2)O(2)). In the presence of H(2)O(2), ATP at concentrations of 100 and 300 microM inhibited Tumour Necrosis factor-alpha (TNF-alpha) release and stimulated IL-10 release in LPS-PHA stimulated whole blood. Moreover, electron spin resonance (ESR) measurements showed that ATP and its breakdown product Adenosine-5'-diphosphate (ADP) attenuated spin trap-hydroxyl radical adduct formation in the Fenton reaction. Our results demonstrate that even in circumstances of severe oxidative stress, ATP has marked anti-inflammatory properties in stimulated whole blood. Moreover, the inhibition of the hydroxyl radical ESR signal indicates a direct attenuation of oxidative stress by ATP.

Adenosine Triphosphate↗

Influence of infrarenal neck length on outcome of endovascular abdominal aortic aneurysm repair.

PURPOSE: To evaluate the influence of the infrarenal neck length on clinical outcome after endovascular abdominal aortic aneurysm repair (EVAR). METHODS: Data were analyzed from 3499 patients enrolled in the EUROSTAR registry between January 1999 and April 2005 who underwent EVAR with a Talent or Zenith endograft and had detailed morphological data recorded. The study cohort was divided into 3 groups according to infrarenal neck length: >15 mm (reference group A, n=2822), 11 to 15 mm (group B, n=485), and < or =10 mm (group C, n=192). Uni- and multivariate analyses were performed to evaluate differences in clinical outcomes among the study groups. RESULTS: After correction for confounders, proximal type I endoleak within 30 days occurred in 10.9% of group C compared to 2.6% of group A (OR 4.46, 95% CI 2.61 to 7.61). Within 48 months of follow-up (median 12 months), the incidence of proximal endoleaks was higher in groups B (9.6%; HR 1.98, 95% CI 1.16 to 3.38) and C (11.3%; HR 2.132, 95% CI 1.17 to 4.60) compared to group A (3.4%). CONCLUSION: Our study indicates that endovascular treatment of abdominal aortic aneurysms with infrarenal neck length <15 mm is associated with significantly increased risk of short- and midterm proximal endoleaks after EVAR. The greater risk of proximal endoleaks should be weighed against the risks of alternative treatment modalities.

Aged↗

Fruit consumption of boys (8--11 years) is related to preferences for sour taste.

The present study investigated whether the most preferred balance between sweet and sour taste of children (n=50, 9.2+/-0.9 yrs of age) are related to their consumption of fruit. Taste preferences were measured with a rank-by-elimination procedure with seven sweet orangeades that differed in added citric acid (i.e. 0.009-0.065 M). Fruit consumption was assessed with a questionnaire that was completed by the children's parents. Results showed that boys' but not girls' most preferred balance between sweet and sour taste was positively correlated with their consumption of fruit: that is, the more added citric acid was preferred the more fruit was consumed. We conclude that preference for high concentrations of citric acid in a sweet context may be associated with the consumption of fruit in boys. In girls, the optimal balance between sweet and sour taste seems to be of less importance; their consumption of fruit may be more influenced by their parents, availability and health related motives.

Child↗

Health related quality of life assessment instruments: a prospective study on preference and acceptability among cancer patients referred for radiotherapy.

The aim of this study was to determine the preferences for and acceptability of existing Quality of Life (QoL) questionnaires among cancer patients. Sixty-two patients completed a set of questionnaires. Criteria were the percentage of missing values, difficult items and the preferences for the answer options. Results indicated small proportions of missing values and difficult items for the EORTC QLQ-C30, the MFI, RSCL, and the MQ (0.0-1.0%). Considerably higher proportions of missing values and difficult items were found for the VAS and the PFS (2.5-3.4%). The answer option of the RSCL subscale 'activity level' was most preferred (29% of subjects), whereas the VAS and PFS were least preferred (19% and 21%, respectively). Our results indicate that patients prefer answer categories that have descriptors in words or a narrow range of answer options, rather than non-described answer options or a broad range of answer options per question.

Aged↗

Dietary intervention in prostate cancer patients: PSA response in a randomized double-blind placebo-controlled study.

The objective of this study was to show or to exclude an effect of dietary supplement on rising prostate-specific antigen (PSA) levels. We have studied the effect of a dietary supplement (verum, administered for 6 weeks) containing plant estrogens, antioxidants, including carotenoids, selenium and other putative prostate cancer inhibiting substances in a randomized placebo-controlled double-blind crossover study in 37 hormonally untreated men with prostate cancer and increasing PSA levels. Outcome measures were changes in the rates of change of serum concentrations of total and free PSA and changes in male sex hormone levels. Male sex hormone levels were significantly lower during the verum phase (DHT: -0.11 nmol/L, p = 0.005; testosterone: -1 nmol/L, p = 0.02). Total PSA doubling time was unaffected. Free PSA, which increased during the placebo phase (average doubling time of 68 weeks), decreased during the verum period (average half-life of 13 weeks; p = 0.02). In those men in whom the free androgen index decreased (21 out of 32), a significant decrease in the slopes of both total and free PSA was observed (p = 0.04). Overall total PSA doubling times did not increase significantly during verum. However, the study demonstrates that this dietary intervention reduces DHT and testosterone levels and increases free PSA doubling time (and total PSA doubling time in a relevant subgroup). If future studies confirm that these observations translate into a slowing of disease progression, a dietary intervention may become an attractive option for prostate cancer treatment and prevention.

Aged↗

Immunoregulatory effects of adenosine 5'-triphosphate on cytokine release from stimulated whole blood.

In vitro studies suggest that extracellular nucleotides and nucleosides may be important regulators of inflammatory and immune responses. Most studies with adenosine 5'-triphosphate (ATP) have been performed in cell lines, which are remote from the human situation. The purpose of the present study was to determine the effects of ATP on TNF-alpha, IL-6 and IL-10 release in stimulated whole blood. Blood samples were drawn from healthy volunteers and incubated with ATP and lipopolysaccharide (LPS) + phytohemagglutinin (PHA) for 24 h. Contrary to expectations, ATP at 100 microM and 300 microM induced a reduction in TNF-alpha secretion by 32+/-8% (mean +/- SEM) and 65+/-4%, respectively. Furthermore, these ATP concentrations induced an increase in IL-10 secretion by 48+/-5% and 62+/-7% in whole blood. The ATP analogue adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S) and adenosine 5'-diphosphate (ADP) also inhibited TNF-alpha release, but only ADP showed a stimulatory effect on IL-10. Co-treatment with adenosine deaminase did not reverse the ATP effect on TNF-alpha and IL-10. These results show, for the first time, that ATP inhibits the inflammatory response in stimulated whole blood as indicated by inhibition of TNF-alpha and stimulation of IL-10 release and that this effect is predominantly mediated by ATP and not by adenosine.

Adenosine Triphosphate↗

Long-term consumption of a raw food diet is associated with favorable serum LDL cholesterol and triglycerides but also with elevated plasma homocysteine and low serum HDL cholesterol in humans.

High consumption of vegetables and fruits is associated with reduced risk for cardiovascular disease. However, little information is available about diets based predominantly on consumption of fruits and their health consequences. We investigated the effects of an extremely high dietary intake of raw vegetables and fruits (70-100% raw food) on serum lipids and plasma vitamin B-12, folate, and total homocysteine (tHcy). In a cross-sectional study, the lipid, folate, vitamin B-12, and tHcy status of 201 adherents to a raw food diet (94 men and 107 women) were examined. The participants consumed approximately 1500-1800 g raw food of plant origin/d mainly as vegetables or fruits. Of the participants, 14% had high serum LDL cholesterol concentrations, 46% had low serum HDL cholesterol, and none had high triglycerides. Of raw food consumers, 38% were vitamin B-12 deficient, whereas 12% had an increased mean corpuscular volume (MCV). Plasma tHcy concentrations were correlated with plasma vitamin B-12 concentrations (r = -0.450, P < 0.001), but not with plasma folate. Plasma tHcy and MCV concentrations were higher in those in the lowest quintile of consumption of food of animal origin (P(trend) < 0.001). This study indicates that consumption of a strict raw food diet lowers plasma total cholesterol and triglyceride concentrations, but also lowers serum HDL cholesterol and increases tHcy concentrations due to vitamin B-12 deficiency.

Adult↗

Etiology of atopy in infancy: the KOALA Birth Cohort Study.

The aim of the KOALA Birth Cohort Study in the Netherlands is to identify factors that influence the clinical expression of atopic disease with a main focus on lifestyle (e.g., anthroposophy, vaccinations, antibiotics, dietary habits, breastfeeding and breast milk composition, intestinal microflora composition, infections during the first year of life, and gene-environment interaction). The recruitment of pregnant women started in October 2000. First, participants with 'conventional lifestyles' (n = 2343) were retrieved from an ongoing prospective cohort study (n = 7020) on pregnancy-related pelvic girdle pain. In addition, pregnant women (n = 491) with 'alternative lifestyles' with regard to child rearing practices, dietary habits (organic, vegetarian), vaccination schemes and/or use of antibiotics, were recruited through organic food shops, anthroposophic doctors and midwives, Steiner schools, and dedicated magazines. All participants were enrolled between 14 and 18 wk of gestation and completed an intake questionnaire on family history of atopy and infant care intentions. Documentation of other relevant variables started in the pregnant mother and covered the first and third trimester as well as early childhood by repeated questionnaires at 14-18, 30, and 34 wk of gestation and 3, 7, 12, and 24 months post-partum. A subgroup of participants, including both conventional and alternative lifestyles, was asked to consent to maternal blood sampling, breast milk and a faecal sample of the infant at 1 month post-partum, capillary blood at age 1 yr, venous blood and observation of manifestation of atopic dermatitis during home visits at the age of 2 yr (using the UK working party criteria and the severity scoring of atopic dermatitis index), and buccal swabs for DNA isolation from child-parent trios. From the start, ethical approval and informed consent procedures included gene-environment interaction studies. Follow-up at 3 and 7 months post-partum was completed with high response rates (respectively 90% and 88% in the conventional group, and 97% and 97% in the alternative group). The home visits at 2 yr of age will be completed in 2005. Preliminary results show that we have succeeded in recruiting a large population with various lifestyle choices with a fairly large contrast with regard to dietary habits (including organic foods, vegetarian diet), vaccination schemes and/or use of antibiotics. We have also been able to collect a large number of faecal samples (n = 1176) and capillary blood samples at age 1 yr (n = 956). Furthermore, a large proportion of the participants have consented with genetic studies. Mid 2006 we expect to report our first results on the relationship between the various exposures in early life and childhood atopy. An outline of the focus and design of the KOALA Birth Cohort Study is presented.

Anthroposophy↗

Reproducibility, validity, and responsiveness to change of a short questionnaire for measuring fruit and vegetable intake.

The reproducibility, relative validity, and responsiveness to change of an eight-item food frequency questionnaire designed to measure fruit and vegetable consumption was assessed among 157 women (mean age = 41 years) in the Netherlands from spring 2001 to spring 2002. Plasma concentrations of vitamin C and total and specific carotenoids served as biomarkers against which validity was assessed. The questionnaire was completed and biomarker concentrations were determined three times: immediately preceding and following a controlled intervention of 1 month aimed at increasing fruit and vegetable consumption and 1 year after the start of the intervention. The 1-month and 1-year reproducibility of total fruit and vegetable consumption assessed in the control group was 0.80 and 0.79 (Spearman's r ). Correlations between consumption and plasma carotenoids and vitamin C at baseline were 0.39 and 0.37, respectively, for fruits and 0.24 and 0.26, respectively, for vegetables. Correlations between changes in consumption and plasma carotenoids and vitamin C were 0.32 and 0.33, respectively, for fruits and 0.28 and 0.30, respectively, for vegetables. On the basis of similar correlations reported in the literature, the authors conclude that the questionnaire appears to be suitable for ranking individuals according to their consumption of fruits and vegetables and according to changes in their consumption. However, the validity of the questionnaire remains to be established in males, other age groups, and populations of lower educational levels.

Adult↗

Long-term ovo-lacto vegetarian diet impairs vitamin B-12 status in pregnant women.

A well-planned vegetarian diet has been stated to be adequate during pregnancy. The aim of the present study was to compare serum vitamin B-12 and homocysteine concentrations in pregnant women (n = 109) consuming vegetarian and Western diets and to evaluate the adequacy of current dietary reference intakes of vitamin B-12 for these women. Pregnant women adhering to vegetarian diets for at least 3 y, with subgroups of ovo-lacto vegetarians (OLVs; n = 27), low-meat eaters (LME, n = 43), and women eating an average Western diet (control group, n = 39), were recruited. Dietary vitamin B-12 intake, serum vitamin B-12, and plasma total homocysteine (tHcy) concentrations were measured in wk 9-12, 20-22, and 36-38 of pregnancy. During pregnancy serum vitamin B-12 concentrations of ovo-lacto vegetarians (P < 0.001) and low-meat eaters (P = 0.050) were lower than those of the control group. We observed the combination of low serum vitamin B-12 concentrations and elevated plasma tHcy in 22% of ovo-lacto vegetarians, in 10% of low-meat eaters, and in 3% of controls (P = 0.003). In OLVs, serum vitamin B-12 predicted 60% of the plasma tHcy variation (P < 0.001), but in LMEs and controls only <10% (NS). Serum vitamin B-12 concentrations increased and plasma tHcy decreased sharply with increasing dietary intake of vitamin B-12 toward a cutoff point of 3 mug/d. Pregnant women consuming a long-term predominantly vegetarian diet have an increased risk of vitamin B-12 deficiency. Current recommended dietary intakes urgently need reevaluation.

Adult↗

Energy restriction and the risk of spontaneous mammary tumors in mice: a meta-analysis.

Our meta-analysis was aimed at providing a systematic review of the literature regarding the effect of energy restriction on spontaneous mammary tumors in mice and at providing a more precise pooled (summary) estimate of the risk of mammary tumors. A sensitivity analysis was conducted to obtain insight in potential heterogeneity between the animal studies. A literature search was conducted with the following terms to identify relevant articles: animal studies, mammary tumors, fat restricted, dietary carbohydrates, energy restriction and calorie restriction. A criteria list for the assessment of quality items (i.e., study characteristics) in animal experiments was developed that was intended to quantitatively assess potential factors that underlie heterogeneous results of different animal experiments. Incidence figures were used to calculate the risk difference. The pooled risk difference was calculated by random effects meta regression analysis. Fourteen animal experiments were included in this meta-analysis. Publication bias could not be identified. The pooled risk difference for the 14 studies was -0.55 with a narrow 95% confidence interval (-0.69; -0.41), implying that the energy-restricted animal groups developed 55% less mammary tumors than the control groups. No heterogeneity could be detected between the studies based on study characteristics that included the age of mice at the start of intervention, duration of intervention, allocation of the mice, use of ad libitum control group, fertility of the mice and the type of energy-providing nutrient (fat, carbohydrate or protein). This meta-analysis confirms that energy restriction in itself consistently protects against the development of mammary tumor in mice, irrespective of the type of restricted nutrient or other study characteristics.

Animals↗

Gamma-linolenic acid supplementation for prophylaxis of atopic dermatitis--a randomized controlled trial in infants at high familial risk.

BACKGROUND: Studies suggest that low concentrations of n-6 long-chain polyenes in early life are correlated to atopic disease in later life. OBJECTIVE: The purpose of the study was to investigate the possible preventive effect of gamma-linolenic acid (GLA) supplementation on the development of atopic dermatitis in infants at risk. DESIGN: In a double-blind, randomized, placebo-controlled trial, formula-fed infants (n = 118) with a maternal history of atopic disease received borage oil supplement (containing 100 mg GLA) or sunflower oil supplement as a placebo daily for the first 6 mo of life. Main outcome measures were the incidence of atopic dermatitis in the first year of life (by UK Working Party criteria), the severity of atopic dermatitis (SCORing Atopic Dermatitis; SCORAD), and the total serum immunoglobulin E (IgE) concentration at the age of 1 y. RESULTS: The intention-to-treat analysis showed a favorable trend for severity of atopic dermatitis associated with GLA supplementation ( x+/- SD SCORAD: 6.32 +/- 5.32) in the GLA-supplemented group as compared with 8.28 +/- 6.54 in the placebo group (P = 0.09; P = 0.06 after adjustment for total serum IgE at baseline, age 1 wk), but no significant effects on the other atopic outcomes. The increase in GLA concentrations in plasma phospholipids between baseline and 3 mo was negatively associated with the severity of atopic dermatitis at 1 y (Spearman's correlation coefficient = -0.233, P = 0.013). There was no significant effect on total serum IgE concentration. CONCLUSION: Early supplementation with GLA in children at high familial risk does not prevent the expression of atopy as reflected by total serum IgE, but it tends to alleviate the severity of atopic dermatitis in later infancy in these children.

Dermatitis, Atopic↗

Using a correction factor to correct for overreporting in a food-frequency questionnaire does not improve biomarker-assessed validity of estimates for fruit and vegetable consumption.

To correct for overreporting of fruit and vegetable (FV) consumption in a food-frequency questionnaire, summary questions about consumption of main FV groups are often used to calculate correction factors. This study compared the ability to rank people according to their FV intake of those summary questions and the sum of questions on individual FV items within categories, and of corrected or uncorrected estimates of specific sorts of FV. Healthy middle-age women (n = 161) completed a food-frequency questionnaire about FV consumption during the previous month and gave a single fasting blood sample. Correction factors were calculated as the reported frequency on a summary question divided by the summed frequencies of all items in a category. Plasma carotenoids and vitamin C served as biomarkers of FV consumption. Significant correlations between FV consumption and biomarkers were observed (e.g., Spearman's correlation coefficient r with total carotenoids/vitamin C: 0.32/0.34 for vegetables, 0.30/0.25 for fruits). Summary estimates of cooked, raw and total vegetable consumption correlated higher with biomarkers than sum estimates. For fruits no differences in correlations between sum and summary estimates were observed. Applying a correction factor on the consumption of carrots and total cabbage resulted in lower correlations with relevant biomarkers. For broccoli/cauliflower, Brussels sprouts and citrus fruits, correlations with biomarkers did not change after correction. We conclude that summary questions may suffice to rank individuals according to their intake of main FV categories, and that correction for overreporting of individual FV items is probably not advisable when ranking individuals according to intake of these items.

Adult↗

Randomized clinical trial of adenosine 5'-triphosphate on tumor growth and survival in advanced lung cancer patients.

We recently reported that regular infusions of adenosine 5'-triphosphate (ATP) inhibited loss of body weight and quality of life in patients with non-small cell lung cancer (NSCLC). In the present paper we investigated whether ATP affects tumor growth and survival in the same group of patients. Fifty-eight NSCLC patients (stage IIIB or IV) were randomly assigned to receive either 10 i.v. 30-h ATP infusions every 2-4 weeks over a 24-week period (n = 28) or no ATP (control patients, n = 30). ATP was given for a median of 6.5 infusions. Differences in time to progression and survival between patients in both groups were tested by means of the log-rank test and Cox regression analysis. Forty-nine patients were evaluable for tumor response. None of the evaluable patients showed a complete or partial response. Median time to progression was 3.9 months [95% confidence interval (CI) = 2.3-5.5] in the ATP group compared to 3.0 months (95% CI = 2.4-3.7) in the control group (p = 0.71). Median survival was 5.6 months (95% CI = 1.1-10.1) for the ATP group and 4.7 months (95% CI = 2.6-6.8) for the control group (p = 0.68). ATP treatment was associated with a significant increase in survival in the subgroup of weight-losing patients with stage IIIB NSCLC: in this subgroup, median survival was 9.3 months (95% CI = 2.1-16.5) for ATP-treated patients versus 3.5 months (95% CI = 2.3-4.7) for control patients (between-group difference: p = 0.009). No significant effect of ATP was observed for weight-losing patients with stage IV NSCLC or for weight-stable NSCLC patients. Although ATP as a single therapy does not lead to tumor regression or increased survival in patients with advanced lung cancer, it may prolong survival in weight-losing patients with stage IIIB lung cancer. The latter finding is intriguing, but requires confirmation in larger clinical trials.

Adenosine Triphosphate↗